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LRP-1 as Target of Broad-Specific Antivirals: Benefits, Risks and Challenges
Daniela Isabel Maldonado-Bauzá1, Luis Gabriel González-Lodeiro1, Li Wen2
1Department of Systems Biology, Biomedical Research. Center for Genetic Engineering and Biotechnology, Havana, Cuba.
Abstract:
Low-density lipoprotein receptor-related protein 1 (LRP-1) is a highly pleiotropic protein involved in the regulation of numerous signalling pathways and interacts with more than 70 different ligands, including viral particles. Recent studies have shown that LRP-1 is the receptor for a spectrum of viruses of great relevance to human and animal health. Rift Valley fever virus (RVFV), Oropouche virus (OROV), Severe fever with thrombocytopaenia syndrome virus (SFTSV), Dengue virus (DENV), Sicilian sandfly fever virus (SFSV), La Crosse virus (LACV), Jamestown Canyon virus (JCV), and Chandipura virus (CHPV) interact with LRP-1 for their infection in mammalian hosts cells. They are included in the arbovirus group, provoke acute disease with significant health implications and present a high risk of transmission from their endemic regions. Currently, none of these viruses have a specific antiviral or vaccine for the treatment of the disease, therefore the development of an antiviral blocking LRP-1 functions would have great scope and potential. In this review, we searched for the current evidence of the validation of LRP-1 as a cellular target for a wide range of RNA genome viruses, highlighting common features of these viruses and the regulation of LRP-1 mediated intracellular signalling in different cell types. In addition, the advantages of an antiviral using LRP-1 as molecular target are discussed, along with the risks and challenges involved in blocking its activity.
Insights
Low-density lipoprotein receptor-related protein 1 (LRP-1) is a cellular target for multiple arboviruses, including RVFV and DENV. Blocking LRP-1 offers a potential antiviral strategy against these significant global health threats.
Area of Science:
- Virology
- Cellular Biology
- Immunology
Background:
- Low-density lipoprotein receptor-related protein 1 (LRP-1) is a multifunctional receptor involved in various cellular processes.
- LRP-1 acts as a cellular entry receptor for a diverse range of RNA viruses, including several arboviruses.
Purpose of the Study:
- To review the evidence supporting LRP-1 as a cellular target for RNA viruses.
- To highlight common viral features and LRP-1 signaling pathways.
- To discuss the potential of LRP-1 as an antiviral target.
Main Methods:
- Literature review of studies investigating LRP-1 and viral infections.
- Analysis of viral characteristics and LRP-1 mediated signaling.
- Discussion of antiviral strategies targeting LRP-1.
Main Results:
- LRP-1 mediates the infection of mammalian cells by numerous arboviruses such as RVFV, OROV, SFTSV, DENV, SFSV, LACV, JCV, and CHPV.
- These viruses cause acute diseases with significant public health implications and pose a high transmission risk.
- LRP-1 plays a role in regulating intracellular signaling pathways relevant to viral infection.
Conclusions:
- LRP-1 is a validated cellular target for a broad spectrum of RNA viruses.
- Developing antivirals that block LRP-1 function presents a promising therapeutic avenue.
- Further research is needed to address the challenges and risks associated with LRP-1 inhibition.
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